Zhang Haoyang, Mo Haojie, Li Peng, Zhou Qi, Shen Gang, Sun Jiale
Department of Urology, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Reproductive Medicine Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Medicine (Baltimore). 2025 Mar 21;104(12):e41911. doi: 10.1097/MD.0000000000041911.
Relationships between blood metabolites and urolithiasis have been identified in few previous observational studies, and causality remains uncertain. We tried to examine whether blood metabolites were causally associated with upper and lower urinary stones in this bidirectional Mendelian randomization (MR) study. The causal relationship between 1400 blood metabolites and upper and lower urinary stones was investigated using genome-wide association study data. The primary analysis for causality analysis was the inverse variance weighted method, with 4 other methods used as complementary analyses. Intersection was then conducted to show the shared metabolites between upper and lower urinary tract stones, followed by the MR-Egger intercept test, Cochran Q test, leave-one-out analysis, MR-PRESSO and the linkage disequilibrium score regressions. The metabolic pathway analysis was conducted to identify potential metabolic pathways. Lastly, reverse MR analyses were also performed. We identified 15 metabolites as potential causal predictors of urinary stones in forward MR analyses. These metabolites consisted of 1 azole, 2 carbohydrates, 6 lipids, 1 nucleotide, 1 peptide, 1 urea, and 3 metabolites with unknown chemical properties. Additionally, urinary stones were found to be significantly associated with some of the above metabolites in reverse MR analyses. Metabolic pathway analysis identified several pathways that may be implicated in the development of urolithiasis. This MR study has established a causal relationship between 12 blood metabolites and the risk of upper and lower urinary tract stones. The identification of these blood metabolites provides valuable insights into early screening, prevention, and treatment of urolithiasis.
在以往的少数观察性研究中已确定了血液代谢物与尿石症之间的关系，但因果关系仍不确定。在这项双向孟德尔随机化（MR）研究中，我们试图检验血液代谢物与上尿路和下尿路结石之间是否存在因果关联。利用全基因组关联研究数据，研究了1400种血液代谢物与上尿路和下尿路结石之间的因果关系。因果关系分析的主要方法是逆方差加权法，另外使用4种方法作为补充分析。然后进行交叉分析以显示上尿路和下尿路结石之间的共享代谢物，随后进行MR-Egger截距检验、 Cochr an Q检验、留一法分析、MR-PRESSO和连锁不平衡评分回归。进行代谢途径分析以确定潜在的代谢途径。最后，还进行了反向MR分析。在正向MR分析中，我们确定了15种代谢物作为尿路结石的潜在因果预测因子。这些代谢物包括1种唑类、2种碳水化合物、6种脂质、1种核苷酸、1种肽、1种尿素和3种化学性质未知的代谢物。此外，在反向MR分析中发现尿路结石与上述某些代谢物显著相关。代谢途径分析确定了几种可能与尿石症发生有关的途径。这项MR研究已确定了12种血液代谢物与上尿路和下尿路结石风险之间的因果关系。这些血液代谢物的鉴定为尿石症的早期筛查、预防和治疗提供了有价值的见解。
